MRI - Guided Adaptive RadioTHerapy for Reducing XerostomiA in Head and Neck Cancer (MARTHA-trial)

NCT03972072 | Active Not Recruiting DMC

• 1 other identifier: HN01_2019
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

Radiotherapy is the main treatment for locally advanced squamous cell carcinoma of the head and neck (SCCHN). Many advances regarding tumor control and patient survival have been made over the past decades. However, treatment-induced toxicity remains a crucial problem, leading to reduced quality of life and permanent impairment for many survivors. Xerostomia is up to this day the leading cause of late toxicity for these patients. Toxicity has been reduced by implementation of modern image guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT), but the low soft-tissue contrast of routine x-ray image guidance does not allow exact planning adaptation and daily imaging is associated with high radiation exposure. Furthermore, despite the routinely use of IMRT, rates of clinically relevant xerostomia (i.e. grade 2 or worse) are still common and reported in approximately 38%. Recently developed hybrid machines (MRidian®-CE approval since 2016), consisting of a linear accelerator and an integrated low-field MRI, could allow a) better visualization of tumor and organs at risk, such as parotid glands during patient positioning and daily treatment, b) daily imaging without additional radiation exposure, c) narrowest established safety margins for the treatment volumes, and finally d) repetitive adaptation of target volumes according to changes in patient weight and tumor anatomy during the radiotherapy course. These procedures would facilitate a high-precision treatment and help reduce dose exposure of critical structures.

Conditions

Head and Neck Cancer; Xerostomia Due to Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with xerostomia of grade 2 or worse

  will be evaluated by the LENT-SOMA (Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA)) side-effect scale: SOM (1)-(4) (higher score represents higher grade xerostomia), A: objective flow measurement (1) 76-95%, (2) 51-75%, (3) 26-50%, (4) 0-25%

  12 month-follow up

Secondary Outcomes (10)

• Percentage of patients with xerostomia of grade 2 or worse

  6- and 24-months follow up

• Locoregional control rate as defined from treatment start to histologically confirmed tumor progression, persistence or last follow up

  2-years

• Overall survival

  2-years

• Description of Quality of life - scoring 6 months after treatment, assessed according to the general EORTC-quality of life "core" questionnaire QLQ C30 (overall quality of life for cancer patients)

  6 months after treatment

• Description of Head-Neck cancer related symptoms 6 months after treatment, assessed according to the specific EORT-head and neck quality of life supplementary questionnaire HN35

  6 months after treatment

Other Outcomes (4)

• variation of radiomics features (delta radiomics) of the parotid glands

  Up to 9 weeks after enrollment: Images acquired at baseline (i.e. up to 10 days before first radiotherapy fraction, used for radiotherapy planning) and daily radiotherapy treatment (treatment days 1-35, 7 weeks)

• variation of tumor radiomics features (delta radiomics) for tumor control for the definitively irradiated (non-surgically treated) patients

  Up to 9 weeks after enrollment: Images acquired at baseline (i.e. up to 10 days before first radiotherapy fraction, used for radiotherapy planning) and daily radiotherapy treatment (treatment days 1-35, 7 weeks)

• longitudinal inflammation profiling

  Up to 3 months after enrollment (value assessment at baseline, after one week of treatment, last week of treatment and first follow up)

Study Arms (1)

Single Intervention Arm

EXPERIMENTAL

daily imaging for MR-IGRT once weekly offline plan adaptation subjective/objective LENT-SOMA xerostomia-evaluation including flow measurements at baseline, 6 month-, 12 month- and 24 month-follow up EORTC-QoL questionnaires at baseline, 6 month-, 12 month- and 24 month-follow up

Other: Pre-defined MR-linac based IGRT and plan adaptation protocol; Diagnostic Test: salivary flow measurements

Interventions

salivary flow measurements DIAGNOSTIC_TEST

baseline, 6 month-, 12 month- and 24 month-follow up salivary flow measurements and LENT-SOMA subjective/objective evaluation of xerostomia

Single Intervention Arm

Pre-defined MR-linac based IGRT and plan adaptation protocol OTHER

daily MR-imaging/MR guided radiotherapy once weekly offline plan adaptation to a total of 6

Single Intervention Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven squamous cell carcinoma of the oral cavity oro- or hypopharynx or larynx, Stages II-IVB, requiring definitive or postoperative bilateral neck irradiation
• Age ≥ 18 years, no upper age limit
• ECOG-Performance score \< 2
• The trial is open to both genders
• History/physical examination within 30 days prior to registration by head and neck surgeon and Radiation Oncologist
• FDG-PET-CT-scan within 30 days prior to registration

You may not qualify if:

• Not adequately controlled hepatitis or HIV disease (HIV-viral load detectable)
• Second non-controlled malignancy other than basalioma or cervical/genital/anal in situ neoplasia during the last 2 years before enrollment
• Bilirubin \> 2,0 mg/dl, SGOT, SGPT, AP, Gamma-GT \>3x norm, GFR \< 30 ml/min
• leucocytes \<3,5 x 10\^9/l or platelets \< 100 x 10\^9/l or neutrophiles \< 1,5 x 10\^9/l
• Other severe comorbidities or psychic disorders (e.g. myocardial infraction within 6 months prior to registration, permanent cardiac arrhythmia, COPD Gold IV, hepatitis B/C, schizophrenia, ongoing alcohol abuse etc.)
• Lactating and pregnant women
• Previous radiotherapy of the neck
• Contraindications for MRI (e.g. pacemaker/ICD, tattoos, cochlear or other not MR-compatible implants)
• Pre-existing salivary gland disease (e.g. Sjorgen's-syndrome) or xerostomia-inducing medication (e.g. anticholinergic medication like tricyclic antidepressant)
• Claustrophobia

Sponsors & Collaborators

• Panagiotis Balermpas: lead

Study Sites (1)

Zurich University Hospital

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Study Officials

• Panagiotis Balermpas, M.D.

  University Hospital Zurich, Department of Radiation-Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator, Senior Consultant

Study Record Dates

• First Submitted: May 23, 2019
• First Posted: June 3, 2019
• Study Start: October 15, 2019
• Primary Completion: May 21, 2025
• Study Completion: July 31, 2026
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

CH (1)